This competing continuation application describes the evolution of this integrated, multidisciplinary, multidepartmental training program over the past 25 years. The goals of the program remain consistent: to produce a new generation of innovative and effective independent cardiovascular investigators, who will become leaders in scientific areas that contribute to the prevention and treatment of cardiovascular disease. The most noticeable changes in "Cardiovascular Mechanisms: Training in Investigation" reflect the creation of a comprehensive modular curriculum in cardiovascular science. While the cornerstone of the program involves mentored research, all trainees participate in didactic modules in order to develop a broad appreciation for the opportunities and challenges in contemporary cardiovascular research. These didactic sessions are augmented by a monthly journal club that is thematically related to the didactic topic under discussion at the time. All trainees participate in a division-wide research conference held weekly. This conference provides trainees with opportunities to discuss their own work, while simultaneously being exposed to cutting-edge cardiovascular science from other laboratories that address different problems, using different methodologies, but hopefully with a consistent appreciation for developing strong hypotheses, using rigorous scientific methods, and generating high quality, reproducible data. Finally, all trainees are evaluated regularly by their mentors, and their progress is reviewed annually by the larger group of training grant preceptors and an external advisory committee. The major strengths of this program lie in the close interaction of basic and clinical investigators and the collective experience of the preceptors, who over the past 10 years have produced over 100 individuals with full-time academic faculty appointments and/or careers in industry. While their individual success as investigators makes them excellent role models, most important is their commitment to the creation of a culture of discovery that teaches and reinforces the skills and behaviors of the successful scientist in those entrusted to their mentoring. (END OF ABSTRACT)